Editing Allergy (section)

===Genetics===
Allergic diseases are strongly [[Family|familial]]; [[Twin#Monozygotic twins|identical twins]] are likely to have the same allergic diseases about 70% of the time; the same allergy occurs about 40% of the time in [[Twin#Dizygotic twins|non-identical twins]].<ref name="Allergy"/> Allergic parents are more likely to have allergic children<ref name="DeSwert"/> and those children's allergies are likely to be more severe than those in children of non-allergic parents. Some allergies, however, are not consistent along [[Genealogy|genealogies]]; parents who are allergic to peanuts may have children who are allergic to [[ragweed]]. The likelihood of developing allergies is [[Heredity|inherited]] and related to an irregularity in the immune system, but the specific [[allergen]] is not.<ref name=DeSwert/>

The risk of allergic [[Sensitization (immunology)|sensitization]] and the development of allergies varies with age, with young children most at risk.<ref name="Croner"/> Several studies have shown that IgE levels are highest in childhood and fall rapidly between the ages of 10 and 30 years.<ref name=Croner/> The peak prevalence of hay fever is highest in children and young adults and the incidence of asthma is highest in children under 10.<ref>{{cite book |vauthors=Jarvis D, Burney P |chapter=Epidemiology of atopy and atopic disease | veditors = Kay AB |title=Allergy and allergic diseases |publisher=Blackwell Science |location=London |year=1997 |pages=1208–24 |volume=2 }}</ref>

[[Ethnic group|Ethnicity]] may play a role in some allergies; however, racial factors have been difficult to separate from environmental influences and changes due to [[human migration|migration]].<ref name=DeSwert/> It has been suggested that different [[Locus (genetics)|genetic loci]] are responsible for asthma, to be specific, in people of [[Caucasian race|European]], [[Hispanic]], [[Asian people|Asian]], and [[Ethnic groups of Africa|African]] origins.<ref name="African Americans with asthma: genetic insights"/>

Researchers have worked to characterize genes involved in inflammation and the maintenance of mucosal integrity. The identified genes associated with allergic disease severity, progression, and development primarily function in four areas: regulating inflammatory responses ([[IFN-α]], [[TLR-1]], [[Interleukin 13|IL-13]], [[Interleukin 4|IL-4]], IL-5, HLA-G, iNOS), maintaining vascular endothelium and mucosal lining (FLG, PLAUR, CTNNA3, PDCH1, COL29A1), mediating immune cell function (PHF11, H1R, HDC, TSLP, STAT6, RERE, PPP2R3C), and influencing susceptibility to allergic sensitization (e.g., ORMDL3, CHI3L1).<ref name="Frontiers">{{cite journal |last1=Falcon |first1=Robbi Miguel G. |last2=Caoili |first2=Salvador Eugenio C. |title=Immunologic, genetic, and ecological interplay of factors involved in allergic diseases |journal=Frontiers in Allergy |date=2023 |volume=4 |publisher=Frontiers|doi=10.3389/falgy.2023.1215616 |doi-access=free |pmid=37601647 |pmc=10435091 }}</ref>

Multiple studies have investigated the genetic profiles of individuals with predispositions to and experiences of allergic diseases, revealing a complex polygenic architecture. Specific genetic loci, such as MIIP, CXCR4, SCML4, CYP1B1, ICOS, and LINC00824, have been directly associated with allergic disorders.<ref name="Frontiers"/> Additionally, some loci show pleiotropic effects, linking them to both autoimmune and allergic conditions, including PRDM2, G3BP1, HBS1L, and POU2AF1.<ref name="Frontiers"/> These genes engage in shared inflammatory pathways across various epithelial tissues—such as the skin, esophagus, vagina, and lung—highlighting common genetic factors that contribute to the pathogenesis of asthma and other allergic diseases.<ref name="Frontiers"/>

In atopic patients, transcriptome studies have identified IL-13-related pathways as key for eosinophilic airway inflammation and remodeling. That causes the body to experience the type of airflow restriction of allergic asthma.<ref name="Frontiers"/> Expression of genes was quite variable: genes associated with inflammation were found almost exclusively in superficial airways, while genes related to airway remodeling were mainly present in endobronchial biopsy specimens.<ref name="Frontiers"/> This enhanced gene profile was similar across multiple sample sizes – nasal brushing, sputum, endobronchial brushing – demonstrating the importance of eosinophilic inflammation, mast cell degranulation and group 3 innate lymphoid cells in severe adult-onset asthma.<ref name="Frontiers"/> IL-13 is an immunoregulatory cytokine that is made mostly by activated [[T-helper 2 (Th2)]] cells.<ref name="U.S. National Library of Medicine">{{cite web |title=IL13 interleukin 13 [homo sapiens (human)] - gene |url=https://www.ncbi.nlm.nih.gov/gene/3596 |website=National Center for Biotechnology Information |publisher=U.S. National Library of Medicine}}</ref> It is an important cytokine for many steps in B-cell maturation and differentiation, since it increases CD23 and MHC class II molecules, and aids in B-cell isotype switching to IgE.<ref name="Frontiers"/><ref name="U.S. National Library of Medicine"/> IL-13 also suppresses macrophage function by reducing the release of pro-inflammatory cytokines and chemokines.<ref name="U.S. National Library of Medicine"/><ref>{{cite journal |last1=Zhu |first1=Chunhua |last2=Zhang |first2=Aihua |last3=Songming |first3=Huang |last4=Ding |first4=Guixia |last5=Pan |first5=Xiaoqin |last6=Chen |first6=Ronghua |title=Interleukin-13 inhibits cytokines synthesis by blocking nuclear factor-ΚB and c-jun N-terminal kinase in human mesangial cells |journal=Journal of Biomedical Research |date=2010 |volume=24 |issue=4 |pages=308–316 |publisher=U.S. National Library of Medicine|doi=10.1016/S1674-8301(10)60043-7 |pmid=23554645 |pmc=3596597 }}</ref> The more striking thing is that IL-13 is the prime mover in allergen-induced asthma via pathways that are independent of IgE and eosinophils.<ref name="U.S. National Library of Medicine"/>